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  1. Article ; Online: Histone Marks-Dependent Effect on Alternative Splicing: New Perspectives for Targeted Splicing Modulation in Cancer?

    Imbriano, Carol / Belluti, Silvia

    International journal of molecular sciences

    2022  Volume 23, Issue 15

    Abstract: Alternative splicing (AS) is a tightly regulated mechanism that generates the complex human proteome from a small number of genes. ...

    Abstract Alternative splicing (AS) is a tightly regulated mechanism that generates the complex human proteome from a small number of genes.
    MeSH term(s) Alternative Splicing ; Chromatin/genetics ; Histone Code/genetics ; Histones/genetics ; Histones/metabolism ; Humans ; Neoplasms/genetics
    Chemical Substances Chromatin ; Histones
    Language English
    Publishing date 2022-07-27
    Publishing country Switzerland
    Document type Journal Article ; Review
    ZDB-ID 2019364-6
    ISSN 1422-0067 ; 1422-0067 ; 1661-6596
    ISSN (online) 1422-0067
    ISSN 1422-0067 ; 1661-6596
    DOI 10.3390/ijms23158304
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  2. Article: Nuclear Estrogen Receptors in Prostate Cancer: From Genes to Function.

    Belluti, Silvia / Imbriano, Carol / Casarini, Livio

    Cancers

    2023  Volume 15, Issue 18

    Abstract: Estrogens are almost ubiquitous steroid hormones that are essential for development, metabolism, and reproduction. They exert both genomic and non-genomic action through two nuclear receptors (ERα and ERβ), which are transcription factors with ... ...

    Abstract Estrogens are almost ubiquitous steroid hormones that are essential for development, metabolism, and reproduction. They exert both genomic and non-genomic action through two nuclear receptors (ERα and ERβ), which are transcription factors with disregulated functions and/or expression in pathological processes. In the 1990s, the discovery of an additional membrane estrogen G-protein-coupled receptor augmented the complexity of this picture. Increasing evidence elucidating the specific molecular mechanisms of action and opposing effects of ERα and Erβ was reported in the context of prostate cancer treatment, where these issues are increasingly investigated. Although new approaches improved the efficacy of clinical therapies thanks to the development of new molecules targeting specifically estrogen receptors and used in combination with immunotherapy, more efforts are needed to overcome the main drawbacks, and resistance events will be a challenge in the coming years. This review summarizes the state-of-the-art on ERα and ERβ mechanisms of action in prostate cancer and promising future therapies.
    Language English
    Publishing date 2023-09-20
    Publishing country Switzerland
    Document type Journal Article ; Review
    ZDB-ID 2527080-1
    ISSN 2072-6694
    ISSN 2072-6694
    DOI 10.3390/cancers15184653
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  3. Article ; Online: Epitranscriptomics as a New Layer of Regulation of Gene Expression in Skeletal Muscle: Known Functions and Future Perspectives.

    Imbriano, Carol / Moresi, Viviana / Belluti, Silvia / Renzini, Alessandra / Cavioli, Giorgia / Maretti, Eleonora / Molinari, Susanna

    International journal of molecular sciences

    2023  Volume 24, Issue 20

    Abstract: Epitranscriptomics refers to post-transcriptional regulation of gene expression via RNA modifications and editing that affect RNA functions. Many kinds of modifications of mRNA have been described, among which are N6-methyladenosine (m6A), N1- ... ...

    Abstract Epitranscriptomics refers to post-transcriptional regulation of gene expression via RNA modifications and editing that affect RNA functions. Many kinds of modifications of mRNA have been described, among which are N6-methyladenosine (m6A), N1-methyladenosine (m1A), 7-methylguanosine (m7G), pseudouridine (
    MeSH term(s) Humans ; Gene Expression Regulation ; RNA/metabolism ; RNA, Messenger/genetics ; RNA, Messenger/metabolism ; Cell Differentiation ; Muscle, Skeletal/metabolism ; RNA Processing, Post-Transcriptional
    Chemical Substances RNA (63231-63-0) ; RNA, Messenger
    Language English
    Publishing date 2023-10-13
    Publishing country Switzerland
    Document type Journal Article ; Review
    ZDB-ID 2019364-6
    ISSN 1422-0067 ; 1422-0067 ; 1661-6596
    ISSN (online) 1422-0067
    ISSN 1422-0067 ; 1661-6596
    DOI 10.3390/ijms242015161
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  4. Article: Alternative Splicing of Transcription Factors Genes in Muscle Physiology and Pathology.

    Imbriano, Carol / Molinari, Susanna

    Genes

    2018  Volume 9, Issue 2

    Abstract: Skeletal muscle formation is a multi-step process that is governed by complex networks of transcription factors. The regulation of their functions is in turn multifaceted, including several mechanisms, among them alternative splicing (AS) plays a primary ...

    Abstract Skeletal muscle formation is a multi-step process that is governed by complex networks of transcription factors. The regulation of their functions is in turn multifaceted, including several mechanisms, among them alternative splicing (AS) plays a primary role. On the other hand, altered AS has a role in the pathogenesis of numerous muscular pathologies. Despite these premises, the causal role played by the altered splicing pattern of transcripts encoding myogenic transcription factors in neuromuscular diseases has been neglected so far. In this review, we systematically investigate what has been described about the AS patterns of transcription factors both in the physiology of the skeletal muscle formation process and in neuromuscular diseases, in the hope that this may be useful in re-evaluating the potential role of altered splicing of transcription factors in such diseases.
    Language English
    Publishing date 2018-02-19
    Publishing country Switzerland
    Document type Journal Article ; Review
    ZDB-ID 2527218-4
    ISSN 2073-4425
    ISSN 2073-4425
    DOI 10.3390/genes9020107
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  5. Article ; Online: Transcription Factors in Cancer: When Alternative Splicing Determines Opposite Cell Fates.

    Belluti, Silvia / Rigillo, Giovanna / Imbriano, Carol

    Cells

    2020  Volume 9, Issue 3

    Abstract: Alternative splicing (AS) is a finely regulated mechanism for transcriptome and proteome diversification in eukaryotic cells. Correct balance between AS isoforms takes part in molecular mechanisms that properly define spatiotemporal and tissue specific ... ...

    Abstract Alternative splicing (AS) is a finely regulated mechanism for transcriptome and proteome diversification in eukaryotic cells. Correct balance between AS isoforms takes part in molecular mechanisms that properly define spatiotemporal and tissue specific transcriptional programs in physiological conditions. However, several diseases are associated to or even caused by AS alterations. In particular, multiple AS changes occur in cancer cells and sustain the oncogenic transcriptional program. Transcription factors (TFs) represent a key class of proteins that control gene expression by direct binding to DNA regulatory elements. AS events can generate cancer-associated TF isoforms with altered activity, leading to sustained proliferative signaling, differentiation block and apoptosis resistance, all well-known hallmarks of cancer. In this review, we focus on how AS can produce TFs isoforms with opposite transcriptional activities or antagonistic functions that severely impact on cancer biology. This summary points the attention to the relevance of the analysis of TFs splice variants in cancer, which can allow patients stratification despite the presence of interindividual genetic heterogeneity. Recurrent TFs variants that give advantage to specific cancer types not only open the opportunity to use AS transcripts as clinical biomarkers but also guide the development of new anti-cancer strategies in personalized medicine.
    MeSH term(s) Alternative Splicing/genetics ; Cell Lineage/genetics ; DNA/metabolism ; Humans ; Models, Biological ; Neoplasms/genetics ; Neoplasms/pathology ; Transcription Factors/metabolism
    Chemical Substances Transcription Factors ; DNA (9007-49-2)
    Language English
    Publishing date 2020-03-20
    Publishing country Switzerland
    Document type Journal Article ; Research Support, Non-U.S. Gov't ; Review
    ZDB-ID 2661518-6
    ISSN 2073-4409 ; 2073-4409
    ISSN (online) 2073-4409
    ISSN 2073-4409
    DOI 10.3390/cells9030760
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  6. Article ; Online: Discovery of potent pyrrolo-pyrimidine and purine HDAC inhibitors for the treatment of advanced prostate cancer.

    Moi, Davide / Bonanni, Davide / Belluti, Silvia / Linciano, Pasquale / Citarella, Andrea / Franchini, Silvia / Sorbi, Claudia / Imbriano, Carol / Pinzi, Luca / Rastelli, Giulio

    European journal of medicinal chemistry

    2023  Volume 260, Page(s) 115730

    Abstract: The development of drugs for the treatment of advanced prostate cancer (PCA) remains a challenging task. In this study we have designed, synthesized and tested twenty-nine novel HDAC inhibitors based on three different zinc binding groups ( ... ...

    Abstract The development of drugs for the treatment of advanced prostate cancer (PCA) remains a challenging task. In this study we have designed, synthesized and tested twenty-nine novel HDAC inhibitors based on three different zinc binding groups (trifluoromethyloxadiazole, hydroxamic acid, and 2-mercaptoacetamide). These warheads were conveniently tethered to variously substituted phenyl linkers and decorated with differently substituted pyrrolo-pyrimidine and purine cap groups. Remarkably, most of the compounds showed nanomolar inhibitory activity against HDAC6. To provide structural insights into the Structure-Activity Relationships (SAR) of the investigated compounds, docking of representative inhibitors and molecular dynamics of HDAC6-inhibitor complexes were performed. Compounds of the trifluoromethyloxadiazole and hydroxamic acid series exhibited promising anti-proliferative activities, HDAC6 targeting in PCA cells, and in vitro tumor selectivity. Representative compounds of the two series were tested for solubility, cell permeability and metabolic stability, demonstrating favorable in vitro drug-like properties. The more interesting compounds were subjected to migration assays, which revealed that compound 13 and, to a lesser extent, compound 15 inhibited the invasive behaviour of androgen-sensitive and -insensitive advanced prostate cancer cells. Compound 13 was profiled against all HDACs and found to inhibit all members of class II HDACs (except for HDAC10) and to be selective with respect to class I and class IV HDACs. Overall, compound 13 combines potent inhibitory activity and class II selectivity with favorable drug-like properties, an excellent anti-proliferative activity and marked anti-migration properties on PCA cells, making it an excellent lead candidate for further optimization.
    MeSH term(s) Male ; Humans ; Histone Deacetylase Inhibitors/pharmacology ; Prostatic Neoplasms/drug therapy ; Purines ; Pyrimidines/pharmacology ; Hydroxamic Acids ; Histone Deacetylases
    Chemical Substances Histone Deacetylase Inhibitors ; Purines ; Pyrimidines ; Hydroxamic Acids ; HDAC10 protein, human (EC 3.5.1.98) ; Histone Deacetylases (EC 3.5.1.98)
    Language English
    Publishing date 2023-08-16
    Publishing country France
    Document type Journal Article
    ZDB-ID 188597-2
    ISSN 1768-3254 ; 0009-4374 ; 0223-5234
    ISSN (online) 1768-3254
    ISSN 0009-4374 ; 0223-5234
    DOI 10.1016/j.ejmech.2023.115730
    Database MEDical Literature Analysis and Retrieval System OnLINE

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    In stock of ZB MED Cologne/Königswinter

    Zs.B 784: Show issues Location:
    Je nach Verfügbarkeit (siehe Angabe bei Bestand)
    bis Jg. 2021: Bestellungen von Artikeln über das Online-Bestellformular
    ab Jg. 2022: Lesesaal (EG)

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  7. Article: Corrigendum: Histone deacetylase functions and therapeutic implications for adult skeletal muscle metabolism.

    Molinari, Susanna / Imbriano, Carol / Moresi, Viviana / Renzini, Alessandra / Belluti, Silvia / Lozanoska-Ochser, Biliana / Gigli, Giuseppe / Cedola, Alessia

    Frontiers in molecular biosciences

    2023  Volume 10, Page(s) 1201886

    Abstract: This corrects the article DOI: 10.3389/fmolb.2023.1130183.]. ...

    Abstract [This corrects the article DOI: 10.3389/fmolb.2023.1130183.].
    Language English
    Publishing date 2023-04-20
    Publishing country Switzerland
    Document type Published Erratum
    ZDB-ID 2814330-9
    ISSN 2296-889X
    ISSN 2296-889X
    DOI 10.3389/fmolb.2023.1201886
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  8. Article: Histone deacetylase functions and therapeutic implications for adult skeletal muscle metabolism.

    Molinari, Susanna / Imbriano, Carol / Moresi, Viviana / Renzini, Alessandra / Belluti, Silvia / Lozanoska-Ochser, Biliana / Gigli, Giuseppe / Cedola, Alessia

    Frontiers in molecular biosciences

    2023  Volume 10, Page(s) 1130183

    Abstract: Skeletal muscle is a highly adaptive organ that sustains continuous metabolic changes in response to different functional demands. Healthy skeletal muscle can adjust fuel utilization to the intensity of muscle activity, the availability of nutrients and ... ...

    Abstract Skeletal muscle is a highly adaptive organ that sustains continuous metabolic changes in response to different functional demands. Healthy skeletal muscle can adjust fuel utilization to the intensity of muscle activity, the availability of nutrients and the intrinsic characteristics of muscle fibers. This property is defined as metabolic flexibility. Importantly, impaired metabolic flexibility has been associated with, and likely contributes to the onset and progression of numerous pathologies, including sarcopenia and type 2 diabetes. Numerous studies involving genetic and pharmacological manipulations of histone deacetylases (HDACs)
    Language English
    Publishing date 2023-03-15
    Publishing country Switzerland
    Document type Journal Article ; Review
    ZDB-ID 2814330-9
    ISSN 2296-889X
    ISSN 2296-889X
    DOI 10.3389/fmolb.2023.1130183
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  9. Article ; Online: Development of Stable Amino-Pyrimidine-Curcumin Analogs: Synthesis, Equilibria in Solution, and Potential Anti-Proliferative Activity.

    Mari, Matteo / Boniburini, Matteo / Tosato, Marianna / Rigamonti, Luca / Cuoghi, Laura / Belluti, Silvia / Imbriano, Carol / Avino, Giulia / Asti, Mattia / Ferrari, Erika

    International journal of molecular sciences

    2023  Volume 24, Issue 18

    Abstract: With the clear need for better cancer treatment, naturally occurring molecules represent a powerful inspiration. Recently, curcumin has attracted attention for its pleiotropic anticancer activity in vitro, especially against colorectal and prostate ... ...

    Abstract With the clear need for better cancer treatment, naturally occurring molecules represent a powerful inspiration. Recently, curcumin has attracted attention for its pleiotropic anticancer activity in vitro, especially against colorectal and prostate cancer cells. Unfortunately, these encouraging results were disappointing in vivo due to curcumin's low stability and poor bioavailability. To overcome these issues, herein, the synthesis of eight new pyrimidine-curcumin derivatives is reported. The compounds were fully characterized (
    MeSH term(s) Male ; Humans ; Curcumin/pharmacology ; Biological Availability ; Antihypertensive Agents ; Antimetabolites ; Cell Survival
    Chemical Substances Curcumin (IT942ZTH98) ; Antihypertensive Agents ; Antimetabolites
    Language English
    Publishing date 2023-09-11
    Publishing country Switzerland
    Document type Journal Article
    ZDB-ID 2019364-6
    ISSN 1422-0067 ; 1422-0067 ; 1661-6596
    ISSN (online) 1422-0067
    ISSN 1422-0067 ; 1661-6596
    DOI 10.3390/ijms241813963
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  10. Article ; Online: Polymer-lipid hybrid nanomedicines to deliver siRNA in and against glioblastoma cells.

    Rinaldi, Arianna / Dumas, Florence / Duskey, Jason Thomas / Imbriano, Carol / Belluti, Silvia / Roy, Charlotte / Ottonelli, Ilaria / Vandelli, Maria Angela / Ruozi, Barbara / Garcion, Emmanuel / Tosi, Giovanni / Boury, Frank

    International journal of pharmaceutics

    2024  Volume 654, Page(s) 123994

    Abstract: Small interfering RNA (siRNA) holds great potential to treat many difficult-to-treat diseases, but its delivery remains the central challenge. This study aimed at investigating the suitability of polymer-lipid hybrid nanomedicines (HNMeds) as novel siRNA ...

    Abstract Small interfering RNA (siRNA) holds great potential to treat many difficult-to-treat diseases, but its delivery remains the central challenge. This study aimed at investigating the suitability of polymer-lipid hybrid nanomedicines (HNMeds) as novel siRNA delivery platforms for locoregional therapy of glioblastoma. Two HNMed formulations were developed from poly(lactic-co-glycolic acid) polymer and a cationic lipid: 1,2-dioleoyl-3-trimethylammonium-propane (DOTAP) or 3ß-[N-(N',N'-dimethylaminoethane)-carbamoyl]cholesterol (DC-Chol). After characterization of the HNMeds, a model siRNA was complexed onto their surface to form HNMed/siRNA complexes. The physicochemical properties and siRNA binding ability of complexes were assessed over a range of nitrogen-to-phosphate (N/P) ratios to optimize the formulations. At the optimal N/P ratio of 10, complexes effectively bound siRNA and improved its protection from enzymatic degradation. Using the NIH3T3 mouse fibroblast cell line, DOTAP-based HNMeds were shown to possess higher cytocompatibility in vitro over the DC-Chol-based ones. As proof-of-concept, uptake and bioefficacy of formulations were also assessed in vitro on U87MG human glioblastoma cell line expressing luciferase gene. Complexes were able to deliver anti-luciferase siRNA and induce a remarkable suppression of gene expression. Noteworthy, the effect of DOTAP-based formulation was not only about three-times higher than DC-Chol-based one, but also comparable to lipofectamine model transfection reagent. These findings set the basis to exploit this nanosystem for silencing relevant GB-related genes in further in vitro and in vivo studies.
    MeSH term(s) Mice ; Animals ; Humans ; Liposomes/chemistry ; Polymers/chemistry ; RNA, Small Interfering ; Glioblastoma/genetics ; Glioblastoma/therapy ; NIH 3T3 Cells ; Nanomedicine ; Lipids/chemistry ; Quaternary Ammonium Compounds ; Fatty Acids, Monounsaturated
    Chemical Substances Liposomes ; 1,2-dioleoyloxy-3-(trimethylammonium)propane (MR86K0XRQP) ; Polymers ; RNA, Small Interfering ; Lipids ; Quaternary Ammonium Compounds ; Fatty Acids, Monounsaturated
    Language English
    Publishing date 2024-03-12
    Publishing country Netherlands
    Document type Journal Article
    ZDB-ID 428962-6
    ISSN 1873-3476 ; 0378-5173
    ISSN (online) 1873-3476
    ISSN 0378-5173
    DOI 10.1016/j.ijpharm.2024.123994
    Database MEDical Literature Analysis and Retrieval System OnLINE

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    In stock of ZB MED Cologne/Königswinter

    Zs.A 1409: Show issues Location:
    Je nach Verfügbarkeit (siehe Angabe bei Bestand)
    bis Jg. 1994: Bestellungen von Artikeln über das Online-Bestellformular
    Jg. 1995 - 2021: Lesesall (1.OG)
    ab Jg. 2022: Lesesaal (EG)

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